Endoproteolytic conversion of beta-endorphin-1-31 to beta-endorphin-1-27 potentiates its central cardioregulatory activity

Brain Res. 1991 May 31;550(1):61-8. doi: 10.1016/0006-8993(91)90405-k.


Brain neurons that express the pro-opiomelanocortin gene secrete multiple forms of beta-endorphin (beta E) which subserve diverse bioregulatory processes. beta E-1-31, for example, is a potent analgetic but beta E-1-27 acts as an opioid antagonist and beta E-1-26, as well as the N-acetyl derivatives of all 3 peptides, lack opioid receptor activity. The present study examines the effects of beta-endorphin processing on its central cardioregulatory potency. Consistent with previous reports, intracisternal beta E-1-31 (1.5 nmol) injection lowered mean arterial pressure (MAP); MAP was reduced by 29.7 +/- 3.9 mm Hg at 60 min and returned toward baseline by 120 min. Unexpectedly, beta E-1-27 displayed a 10-fold greater hypotensive potency than beta E-1-31. At 0.15 nmol, it produced a response equivalent to 1.5 nmol beta E-1-31 while 1.5 nmol beta E-1-27 sustained a maximal reduction in MAP (49.2 +/- 3.9 mm Hg) throughout the 120-min test period. In contrast, beta E-1-26 and N-acetyl-beta E-1-26, -1-27 and -1-31 were inactive at 1.5 nmol. Bradycardia accompanied the depressor response to the higher beta E-1-27 dose but not to beta E-1-31. Naloxone pretreatment completely blocked the depressor effects of both beta E-1-31 and beta E-1-27, and reversed the bradycardia produced by beta E-1-27, suggesting that both peptides act through opioid receptors. beta E-1-27 also stimulated catecholamine release from the perfused adrenal gland but beta E-1-31 was inactive. These findings emphasize the importance of regionally selected post-translational processing in defining the functional specificity of beta E peptides.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / innervation
  • Adrenal Glands / metabolism*
  • Animals
  • Blood Pressure / drug effects*
  • Electric Stimulation
  • Endopeptidases / metabolism*
  • Epinephrine / metabolism*
  • Heart Rate / drug effects*
  • Male
  • Norepinephrine / metabolism*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Inbred Strains
  • Reference Values
  • Stereotaxic Techniques
  • beta-Endorphin / administration & dosage
  • beta-Endorphin / metabolism
  • beta-Endorphin / pharmacology*


  • Peptide Fragments
  • beta-Endorphin
  • beta-endorphin (1-27)
  • Endopeptidases
  • Norepinephrine
  • Epinephrine